Chronic molindone treatment: relative inability to elicit dopamine receptor supersensitivity in rats.
Chronic treatment of rats with the antipsychotic drug molindone (2.5 mg/kg) did not elicit behavioral supersensitivity to apomorphine (AP) (0.25 mg/kg) or increased striatal 3H-spiroperidol binding, whereas treatment with haloperidol (0.5-1.0 mg/kg) produced manifestations of dopaminergic supersensitivity in both paradigms. Chronic treatment with a high dose of molindone (20 mg/kg) elicited a small, but significant increase in behavioral sensitivity to AP (57%) which was, however, significantly less than that produced by 1 mg/kg haloperidol (126%, P less than 0.01). Apparent tolerance to elevation of striatal and frontal cortical 3,4-dihydroxyphenylacetic acid (DOPAC) levels was obtained with chronic molindone treatment (5 or 20 mg/kg). None of the molindone doses used (2.5-50 mg/kg) increased striatal dopamine receptor binding. Scatchard analyses revealed no change in either maximal binding capacity (Bmax) or dissociation constant (Kd). A significant (P less than 0.001) correlation of receptor binding activity and stereotypy score was obtained for haloperidol-, but not molindone-treated rats. These results with molindone in an animal model of tardive dyskinesia suggest that this drug may have a lower potential for eliciting this disorder in humans.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001667:Binding, Competitive; D003342:Corpus Striatum / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008972:Molindone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013134:Spiperone / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects; D013997:Time Factors
D007211:Indoles; D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; D013134:Spiperone; D006220:Haloperidol; D008972:Molindone